A large body of evidence indicates the important role of cellular immunity (CI) in the process of tumor cell destruction. Non-specific mechanisms of potentiating host CI is used with increasing frequency for immunotherapy of a variety of tumors, however, the actual mechanisms of this phenomenon is unexplained. Thus is specific host immunity to the non-specific stimulant required for tumor resistance? Is tumor resistance due to non-specific cytotoxicity inhibition of tumor cell proliferation, or due to an elevated specific anti-tumor immunity? In either case how is the tumor cell killed? We have recently been trying to elucidate some of these questions by using Listeria monocytogenes (LM) as a non-specific stimulant for suppression of non-antigenic tumors in vivo. Due to the biological complexity of the intact host in vitro models offer new approaches for better understanding of mechanisms involved. I have recently developed such a model. The results demonstrate that peritoneal cells from mice injected with LM have the capacity to non-specifically destroy target tumor cells in vitro. The purpose of the present project is to complement the in vivo studies by a stepwise approach to define the cellular and molecular basis of non- specific tumor destruction (NSTD) in vitro. Initial studies underway are to establish optimum methodology followed by a quantifiable radioisotope assay for tumor cell death. Next the effector cell populations involved in NSTD will be defined and purified. This is to be followed by determination of cellular cooperation or synergism and possible role of humoral factors during NSTD. Next the role of soluble mediators of CI or lymphokines if any will be determined followed by their partial purification and influence on effector cells.